68Ga-Pentixafor PET/CT Versus Adrenal Vein Sampling in Diagnosing Unilateral Subtype of Primary Aldosteronism Concurrent With Autonomous Cortisol Secretion (PREDICT)

Official title

68Ga-Pentixafor PET/CT Versus Adrenal Vein Sampling in Diagnosing Unilateral Subtype of Primary Aldosteronism Concurrent With Autonomous Cortisol Secretion (PREDICT): a Randomized Cross-over Trial

Overview

To validate the accuracy of 68Ga-Pentixafor PET/CT and adrenal venous sampling (AVS) in subtype diagnosis of PA/ACS patients with adrenal nodules, based on biochemical and clinical remission outcomes, and to determine whether the diagnostic accuracy of 68Ga-Pentixafor PET/CT is non-inferior to AVS.

Detailed description

This is a prospective, multicenter, randomized crossover trial. Patients with a confirmed diagnosis of primary aldosteronism (PA) or autonomous cortisol secretion (ACS) with adrenal nodules were prospectively enrolled. They were randomized to undergo 68Ga-Pentixafor PET/CT and adrenal venous sampling (AVS) in a crossover design for subtype diagnosis. The treatment strategy was determined based on the diagnostic results, with the primary endpoint being the biochemical complete remission rate at 6 months postoperatively. The study aims to compare the value of these two methods in the subtype diagnosis of PA.

Interventions

• Diagnostic test 68Ga-Pentixafor PET/CT
  Patients in the 68Ga-Pentixafor PET/CT group will first undergo 68Ga-Pentixafor PET/CT, followed by adrenal venous sampling (AVS). The subsequent treatment will be guided based on the diagnostic results. The diagnosis of unilateral PA was made if LISUVmax ≥1.50 or or unilateral functional adrenal tumor based on 68Ga-Pentixafor PET/CT
• Diagnostic test AVS
  Patients in the adrenal venous sampling (AVS) group will first undergo adrenal venous sampling (AVS), followed by 68Ga-Pentixafor PET/CT. The subsequent treatment will be guided based on the diagnostic results. The diagnosis of unilateral PA was made LI ≥ 4 or LI 2-4 with contralateral suppression or typical nodule on the dominant side by CT

Primary outcome measures

• The proportion of complete biochemical remission [Time frame: At 6 months of follow-up]

Secondary outcome measures (5)

• The proportion of complete clinical remission [Time frame: At 6 months of follow-up]
• In surgical population, the proportion of complete biochemical remission [Time frame: At 6 months of follow-up]
• In surgical population, the proportion of complete clinical remission [Time frame: At 6 months of follow-up]
• In surgical population, the accuracy in identifying unilateral primary aldosteronism. [Time frame: At 6 months of follow-up]
• In the surgical treatment group, the remission rate of cortisol autonomous secretion [Time frame: at the 6-month follow-up assessment]

Eligibility criteria

Inclusion criteria

• Getting the written informed consent;
• PA conccurent with autonomous cortisol secretion;
• Patients with hypertension aged 18-70 years;
• CT or MRI scan of the adrenal glands with adenoma. Exclusion criteria

Exclusion criteria

• Unable to complete 68Ga-Pentixafor PET/CT or AVS;
• Refusal of surgery or contraindications for surgery;
• PA patients who meet the by-passing AVS criteria \[i.e., younger than 35 years old, spontaneous hypokalemia, adrenal CT indicated unilateral low-density adenoma (≥1cm), plasma aldosterone >300pg/ml\]
• Suspicion of familial hyperaldosteronism or Liddle syndrome. \[i.e., age <20 years, hypertension and hypokalemia, or with family history\];
• Suspicion of pheochromocytoma or adrenal carcinoma;
• Patients with actively malignant tumor;
• Patients who have adrenalectomy history;
• Long-term use of glucocorticoids;
• Pregnant or lactating women; with alcohol or drug abuse and mental disorders;
• Congestive heart failure with New York Heart Association (NYHA) Functional Classification III or IV; History of serious cardiovascular or cerebrovascular disease (angina, myocardial infarction or stroke) in the past 3 months; Severe anemia (Hb<60g/L); Serious liver dysfunction or chronic kidney disease aspartate aminotransferase (AST) or alanine transaminase (ALT) >3 times the upper limit of normal, or estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2); Systemic Inflammatory Response Syndrome (SIRS); Uncontrolled diabetes (FBG≥13.3 mmol/L); Obesity (BMI≥35 kg/m²) or Underweight (BMI≤18 kg/m²); Untreated aneurysm; Other comorbidity potentially interfering with treatment;
• Suspected PBMAH or PPNAD;
• Poor compliance or any other reason deemed unsuitable for inclusion by the investigators;
• Patients with adrenal insufficiency requiring hormone replacement therapy.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Double blind

Primary purpose

Diagnostic

Study locations

China · 1 center

• The First Affilated Hospital of Chongqing Medical University — Chongqing

Publications

• Ding J, Tong A, Hacker M, Feng M, Huo L, Li X. Usefulness of 68 Ga-Pentixafor PET/CT on Diagnosis and Management of Cushing Syndrome. Clin Nucl Med. 2022 Aug 1;47(8):669-676. doi: 10.1097/RLU.0000000000004244. Epub 2022 Apr 22. PMID 35452014
• Libianto R, Russell GM, Stowasser M, Gwini SM, Nuttall P, Shen J, Young MJ, Fuller PJ, Yang J. Detecting primary aldosteronism in Australian primary care: a prospective study. Med J Aust. 2022 May 2;216(8):408-412. doi: 10.5694/mja2.51438. Epub 2022 Feb 25. PMID 35218017
• Xu Z, Yang J, Hu J, Song Y, He W, Luo T, Cheng Q, Ma L, Luo R, Fuller PJ, Cai J, Li Q, Yang S; Chongqing Primary Aldosteronism Study (CONPASS) Group. Primary Aldosteronism in Patients in China With Recently Detected Hypertension. J Am Coll Cardiol. 2020 Apr 28;75(16):1913-1922. doi: 10.1016/j.jacc.2020.02.052. PMID 32327102
• Inoue K, Kitamoto T, Tsurutani Y, Saito J, Omura M, Nishikawa T. Cortisol Co-Secretion and Clinical Usefulness of ACTH Stimulation Test in Primary Aldosteronism: A Systematic Review and Biases in Epidemiological Studies. Front Endocrinol (Lausanne). 2021 Mar 16;12:645488. doi: 10.3389/fendo.2021.645488. eCollection 2021. PMID 33796078
• Buffolo F, Pieroni J, Ponzetto F, Forestiero V, Rossato D, Fonio P, Nonnato A, Settanni F, Mulatero P, Mengozzi G, Monticone S. Prevalence of Cortisol Cosecretion in Patients With Primary Aldosteronism: Role of Metanephrine in Adrenal Vein Sampling. J Clin Endocrinol Metab. 2023 Aug 18;108(9):e720-e725. doi: 10.1210/clinem/dgad179. PMID 36974473
• Spath M, Korovkin S, Antke C, Anlauf M, Willenberg HS. Aldosterone- and cortisol-co-secreting adrenal tumors: the lost subtype of primary aldosteronism. Eur J Endocrinol. 2011 Apr;164(4):447-55. doi: 10.1530/EJE-10-1070. Epub 2011 Jan 26. PMID 21270113
• Funder JW, Carey RM, Mantero F, Murad MH, Reincke M, Shibata H, Stowasser M, Young WF Jr. The Management of Primary Aldosteronism: Case Detection, Diagnosis, and Treatment: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016 May;101(5):1889-916. doi: 10.1210/jc.2015-4061. Epub 2016 Mar 2. PMID 26934393
• Naruse M, Katabami T, Shibata H, Sone M, Takahashi K, Tanabe A, Izawa S, Ichijo T, Otsuki M, Omura M, Ogawa Y, Oki Y, Kurihara I, Kobayashi H, Sakamoto R, Satoh F, Takeda Y, Tanaka T, Tamura K, Tsuiki M, Hashimoto S, Hasegawa T, Yoshimoto T, Yoneda T, Yamamoto K, Rakugi H, Wada N, Saiki A, Ohno Y, Haze T. Japan Endocrine Society clinical practice guideline for the diagnosis and management of prima PMID 35418526

Identifiers

NCT: NCT06833437 · PREDICT

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗